| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2001: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Research Abstract |
The leves of lysophosphatidylcholine (LPC) in serum of rabbits fed a high-cholesterol diet for 10-12 weeks were 5-6 times higher than those of normal rabbits. The amounts of lysophosphatidic acids (LPA) accumulated in incubated serum (24h, 37℃) of the hypercholesterolemic rabbis increased with the increase in the period for cholesterol-loading. Interestingly, the major molecular species of LPA in the incubated serum of the hypercholesterolemic rabbits was linoleoyl (18:2) -LPA, althogh the levels of five major molecular spesies of LPC incceased production of 18:2-LPA was mainly due to the increase in 18:2-LPC, but not lysophospholipase D itself, in the animal model of atherosclerosis. In addition, LPA was found to activate THP-1 cells, a monocytic cell line, leading to their stimulated attachement to umbilical vein endothelial cells. These results indicate that increased production of LPA in blood circutation of the hypedipidemic rabbits is involved in the progression of atherosclerotic lesions. We deviced a convenient assay method for lysophospholipase D activity, and purifled lysophospholipase D from about 950 mi of human plasma using this method. LC/MS/MS of the peptides of the purified lysophospholipase D with trypsin resulted in its identification as autotaxin, a endo-nucleolide phosphodiesterase. This finding suggests that lysophospholipase Din the circulation may exert diverse functions by hydrolyzing both lysophospholipids and nucleotides.
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